Pressure and life: some biological strategies

All biological processes of life on Earth experience varying degrees of pressure. Aquatic organisms living in the deep-sea, as well as chondrocytic cells of articular cartilage are exposed to hydrostatic pressures that rise up to several hundred times that of atmospheric pressure. In the case of marine larvae that disperse through the oceanic water column, pressure changes might be responsible for stress conditions during development, limiting colonisation capabilities. In a number of biological systems, life strategies may be significantly influenced by pressure. In this review, we will focus on the consequences of pressure changes on various biological processes, and more specifically on animals living in the deep-sea. Revisiting general principles of pressure effects on biological systems, we present recent data illustrating the diversity of effects pressure may have at different levels in biological systems, with particular attention to effects on gene expression. After a review of the main pressure equipments available today for studying species living naturally at high pressure, we summarise what is known concerning pressure impact during animal development.     

Application of chemiluminescent methods in biochemical investigations

The review of modern luminescent methods of research, their prospects and potentialities of practical application in biological researches is presented. Special attention is given to the study of dynamics of the processes of peroxide oxidation and to activity of the enzymes of antioxidant protection in biological systems using the chemiluminescent methods, and also to their use in experimental oncology and radiobiology.     

Isochoric conditions enable high subfreezing temperature pancreatic islet preservation without osmotic cryoprotective agents

While biological systems are typically studied under isobaric (constant pressure) conditions, recent reports on the bio-thermodynamics of isochoric (constant volume) systems point to their potential for subfreezing-temperature preservation of biological matter. This preliminary study, in which we report that pancreatic islets can survive multi-day preservation at high subfreezing temperatures in an isochoric chamber without osmotic cryoprotective agents (CPA), highlights the potential of isochoric cryopreservation in an application of clinical value.     

Free energy of biological systems

The generalization of the Gibbs potential to open spatially inhomogeneous systems is given. This generalization is based on the abandonment of the local equilibrium hypothesis and the introduction of the specific parameters of spatial inhomogeneity: thermodynamical forces and the coordinates of useful works. The existence of the potential state function whose decrease determines the algebraic sum of useful (external) and dissipative (internal) works executed by the system was justified. This function presents the difference between the internal energy of the spatial inhomogeneous system and its homogeneous parts and was named (owing to its independence from the pathways of processes in the space of thermostatic variables) the general thermodynamic potential. It was demonstrated that the application of this potential to biological systems permits one to trace their development for each of their intrinsic degrees of freedom, to combine the thermodynamic and kinetic approaches to the problems of their evolution, to find a criterion of maturity of a biological organism and a general measure of the orderliness of the biosystem, to find the driving forces of biological processes, and confirm the possibility of development of biosystems without the equilibrium state.     

Active Interaction Mapping as a tool to elucidate hierarchical functions of biological processes

Increasingly, various ‘omics data are contributing significantly to our understanding of novel biological processes, but it has not been possible to iteratively elucidate hierarchical functions in complex phenomena. We describe a general systems biology approach called Active Interaction Mapping (AI-MAP), which elucidates the hierarchy of functions for any biological process. Existing and new ‘omics data sets can be iteratively added to create and improve hierarchical models which enhance our understanding of particular biological processes. The best datatypes to further improve an AI-MAP model are predicted computationally. We applied this approach to our understanding of general and selective autophagy, which are conserved in most eukaryotes, setting the stage for the broader application to other cellular processes of interest. In the particular application to autophagy-related processes, we uncovered and validated new autophagy and autophagy-related processes, expanded known autophagy processes with new components, integrated known non-autophagic processes with autophagy and predict other unexplored connections.     

From protein-protein interactions to protein co-expression networks: a new perspective to evaluate large-scale proteomic data

The reductionist approach of dissecting biological systems into their constituents has been successful in the first stage of the molecular biology to elucidate the chemical basis of several biological processes. This knowledge helped biologists to understand the complexity of the biological systems evidencing that most biological functions do not arise from individual molecules; thus, realizing that the emergent properties of the biological systems cannot be explained or be predicted by investigating individual molecules without taking into consideration their relations. Thanks to the improvement of the current -omics technologies and the increasing understanding of the molecular relationships, even more studies are evaluating the biological systems through approaches based on graph theory. Genomic and proteomic data are often combined with protein-protein interaction (PPI) networks whose structure is routinely analyzed by algorithms and tools to characterize hubs/bottlenecks and topological, functional, and disease modules. On the other hand, co-expression networks represent a complementary procedure that give the opportunity to evaluate at system level including organisms that lack information on PPIs. Based on these premises, we introduce the reader to the PPI and to the co-expression networks, including aspects of reconstruction and analysis. In particular, the new idea to evaluate large-scale proteomic data by means of co-expression networks will be discussed presenting some examples of application. Their use to infer biological knowledge will be shown, and a special attention will be devoted to the topological and module analysis.     

Fluorogenic ‘click-on’ dendrimer reporter for rapid profiling of cell proliferation

The application of small molecule fluorescent reporters to monitor biological systems is limited by their poor water solubility and background fluorescence of these reporters. Herein, we describe the synthesis and testing of a fluorogenic ‘click’ dendrimer reporter to monitor cellular processes. The reporter system consists of a polyamidoamine (PAMAM) dendrimer conjugated with 3-azido-7-hydroxy coumarin. After the copper(I)-catalyzed azide–alkyne cycloaddition reaction (‘click’ reaction) with alkyne-derivatized target molecules, the natively non-fluorescent construct has a strong enhancement in fluorescence. This fluorogenic dendrimer reporter can be used to efficiently monitor biological processes and the specificity afforded by the ‘click’ reaction greatly reduces background noise and enhances assay flexibility. We used this fluorogenic dendrimer reporter to monitor incorporation of 5-ethynyl-2′-deoxyuridine (EdU) into newly synthesized DNA, as a surrogate marker of cellular proliferation. We anticipate that this new class of fluorogenic reporter can be used to monitor a wide array of molecules and lends itself to high-throughput profiling of biological systems.     

A scaling model for dichotomous branching processes

We derive an affine scaling law for dichotomous branching processes in biological systems. An application to the human bronchial tree demonstrates good agreement with experimental results.     

A nonlinear model for studying oscillations in the blood pressure control system

The idea that physiological systems sometimes include oscillations as part of their control function is a relatively new idea; the paper discusses the role of such oscillations in the regulation of arterial blood pressure and how they can be studied by modelling techniques. A nonlinear model is proposed which can be related directly to the physiology. This is seen as an important step because mainly previous studies of biological oscillations have used lumped equations, e.g. the Van der Pol equation, which do not possess this property. On the basis of the model, the oscillatory behaviour of the blood pressure control system is analysed by the application of the dual input describing function technique, a powerful analytical method which has wide application to the study of nonlinear oscillatory phenomena in physiology.The final section of the paper considers the digital simulation of the model by Z transform techniques and how the simulation can be used to study the interaction of respiratory and blood pressure control systems.     

Monitoring biological wastewater treatment processes: recent advances in spectroscopy applications

Biological processes based on aerobic and anaerobic technologies have been continuously developed to wastewater treatment and are currently routinely employed to reduce the contaminants discharge levels in the environment. However, most methodologies commonly applied for monitoring key parameters are labor intensive, time-consuming and just provide a snapshot of the process. Thus, spectroscopy applications in biological processes are, nowadays, considered a rapid and effective alternative technology for real-time monitoring though still lacking implementation in full-scale plants. In this review, the application of spectroscopic techniques to aerobic and anaerobic systems is addressed focusing on UV–Vis, infrared, and fluorescence spectroscopy. Furthermore, chemometric techniques, valuable tools to extract the relevant data, are also referred. To that effect, a detailed analysis is performed for aerobic and anaerobic systems to summarize the findings that have been obtained since 2000. Future prospects for the application of spectroscopic techniques in biological wastewater treatment processes are further discussed.     

In vivo bioluminescence imaging for integrated studies of infection

Understanding biological processes in the context of intact organ systems with fine temporal resolution has required the development of imaging strategies that reveal cellular and molecular changes in the living body. Reporter genes that confer optical signatures on a given biological process have been used widely in cell biology and have been used more recently to interrogate biological processes in living animal models of human biology and disease. The use of internal biological sources of light, luciferases, to tag cells, pathogens, and genes has proved to be a versatile tool to provide in vivo indicators that can be detected externally. The application of this technology to the study of animal models of infectious disease has not only provided insights into disease processes, but has also revealed new mechanisms by which pathogens may avoid host defences during infection.     

Stable isotopes in physiological ecology and food web research

Mention the word 'isotopes' and most people will think of short-lived radioactive isotopes. Yet far more abundant than the radioactive forms and perhaps much more useful for ecological studies are the stable isotopes. Early interest in stable isotope analyses developed in the geological sciences, and their application in environmental biology has developed slowly until recently. Over the past few years, innovative applications of stable isotope analyses to studies of biological processes have been expanding rapidly, and there is every indication that stable isotope approaches will lead to major advances over the next decade in our understanding of physiological processes and fluxes through ecological systems. Studies of plant and animal physiological ecology and food webs will benefit greatly.     

生物过程化学机制的单分子荧光探测

单分子荧光检测越来越广泛地被应用于生命科学领域。这项技术可以对生物过程的化学机制进行定量、仔细的探究,与传统系综实验形成很好的互补。本文简介近几年单分子荧光检测研究的若干典型实例,以此展示这项技术的特点、优势及其可能的应用。它们涉及从简单的生化反应到复杂的蛋白表达调控等重要的生物过程。     

计算系统生物学:理论、方法及在药物研发中的应用

计算系统生物学是一个多学科交叉的新兴领域,旨在通过整合海量数据建立其生物系统相互作用的复杂网络。数据的整合和模型的建立需要发展合适的数学方法和软件工具,这也是计算系统生物学的主要任务。生物系统模型有助于从整体上理解生物体的内在功能和特性。同时,生物网络模型在药物研发中的应用也越来越受到制药企业以及新药研发机构的重视,如用于特异性药物作用靶点的预测和药物毒性评估等。该文简要介绍计算系统生物学的常见网络和计算模型,以及建立模型所用的研究方法,并阐述其在建模和分析中的作用及面临的问题和挑战。     

Non-thermal Plasma Activates Human Keratinocytes by Stimulation of Antioxidant and Phase II Pathways

Non-thermal atmospheric pressure plasma provides a novel therapeutic opportunity to control redox-based processes, e.g. wound healing, cancer, and inflammatory diseases. By spatial and time-resolved delivery of reactive oxygen and nitrogen species, it allows stimulation or inhibition of cellular processes in biological systems. Our data show that both gene and protein expression is highly affected by non-thermal plasma. Nuclear factor erythroid-related factor 2 (NRF2) and phase II enzyme pathway components were found to act as key controllers orchestrating the cellular response in keratinocytes. Additionally, glutathione metabolism, which is a marker for NRF2-related signaling events, was affected. Among the most robustly increased genes and proteins, heme oxygenase 1, NADPH-quinone oxidoreductase 1, and growth factors were found. The roles of NRF2 targets, investigated by siRNA silencing, revealed that NRF2 acts as an important switch for sensing oxidative stress events. Moreover, the influence of non-thermal plasma on the NRF2 pathway prepares cells against exogenic noxae and increases their resilience against oxidative species. Via paracrine mechanisms, distant cells benefit from cell-cell communication. The finding that non-thermal plasma triggers hormesis-like processes in keratinocytes facilitates the understanding of plasma-tissue interaction and its clinical application.     

Meta-All: a system for managing metabolic pathway information

Background  

Many attempts are being made to understand biological subjects at a systems level. A major resource for these approaches are biological databases, storing manifold information about DNA, RNA and protein sequences including their functional and structural motifs, molecular markers, mRNA expression levels, metabolite concentrations, protein-protein interactions, phenotypic traits or taxonomic relationships. The use of these databases is often hampered by the fact that they are designed for special application areas and thus lack universality. Databases on metabolic pathways, which provide an increasingly important foundation for many analyses of biochemical processes at a systems level, are no exception from the rule. Data stored in central databases such as KEGG, BRENDA or SABIO-RK is often limited to read-only access. If experimentalists want to store their own data, possibly still under investigation, there are two possibilities. They can either develop their own information system for managing that own data, which is very time-consuming and costly, or they can try to store their data in existing systems, which is often restricted. Hence, an out-of-the-box information system for managing metabolic pathway data is needed.     

New concepts of microbial treatment processes for the nitrogen removal in wastewater

Many countries strive to reduce the emissions of nitrogen compounds (ammonia, nitrate, NOx) to the surface waters and the atmosphere. Since mainstream domestic wastewater treatment systems are usually already overloaded with ammonia, a dedicated nitrogen removal from concentrated secondary or industrial wastewaters is often more cost-effective than the disposal of such wastes to domestic wastewater treatment. The cost-effectiveness of separate treatment has increased dramatically in the past few years, since several processes for the biological removal of ammonia from concentrated waste streams have become available. Here, we review those processes that make use of new concepts in microbiology: partial nitrification, nitrifier denitrification and anaerobic ammonia oxidation (the anammox process). These processes target the removal of ammonia from gases, and ammonium-bicarbonate from concentrated wastewaters (i.e. sludge liquor and landfill leachate). The review addresses the microbiology, its consequences for their application, the current status regarding application, and the future developments.